• 한국환경성돌연변이발암원학회지
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• 제16권2호
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• pp.109-116
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• 1996

To study the effect of dietary $\omega 6/\omega 3$ fatty acid ratios on the preneoplastic lesions and lipid peroxidation in rat hepatocellular chemical carcinogenesis, placental glutathione S-transferase(GST-P) positive foci area and numbers, glucose 6-phosphatase(G6Pase) activity, thiobarbituric acid reactive substances (TBARS) were measured. Male Sprague-Dawley rats were fed 5 different diets-low $\omega 6/\omega 3$ ratio with fish oil (Low-F), low $\omega 6/\omega 3$ ratio with perilia oil(Low-P), moderate ratio with perilia oil(Moderate), blend of 10 different commercial fats and oils(High-BL) and high $\omega 6/\omega 3$ ratio(High)-for 8 weeks. Hepatocarcinogenesis was induced by modified Ito model. The area of GST-P positive loci was the lowest in Moderate group and in ascending order of Low-F < Low-P < High-BL < High. But statistically, only Moderate and High groups were significantly different. The number of GST-P positive foci showed the same trend as foci area. The activities of G6Pase, membrane stability marker, were increased as $\omega 6/\omega 3$ ratio decreased. Lipid peroxidation values (TBARS) were the lowest in Low-F group and it is significantly different from Moderate, High-BL and High groups. When dietary $\omega 6/\omega 3$ ratio was moderate(4.06), hepatocarcinogenesis was suppressed compared with high or low $\omega 6/\omega 3$ ratios. Blend fat, commonly consumed among Koreans, did not show any suppressive effect on carcinogenesis because of high ratio(6.7). These results suggest that dietary $\omega 6/\omega 3$ ratio influences hepatocellular chemical carcinogenesis. It is recommended that appropriate $\omega 6/\omega 3$ ratio should be around 4.0. and we recommend to use more $\omega 3$ fatty acid in food preparation to reduce the risk of hepatocarcinogenesis.

• 한국식품영양과학회지
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• 제28권3호
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• pp.638-645
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• 1999

This study was done to investigate effects of ${\gamma}$ irradiated beef feeding on the formation of gluta thione S transferase placental form positive(GST P+) foci, lipid peroxidation, cytochrome P450 system and microsomal glucose 6 phosphate activity in diethylnitrosamine(DEN) initiated rat hepatocarci nogenesis. Weaning Sprague Dawley male rats were fed the diet containing ${\gamma}$ irradiatied ground beef at the dose of 0, 3, 5kGy as a 20% of protein source for 8 weeks. One week after feeding, rats were intraperitoneally injected twice with a dose of DEN(50mg/kg BW). As a promoter, 0.05% phenobarbital was fed in drinking water from one week after DEN treatment until the end of experiment. At the end of 8th week, rats were sacrificed and hepatic GST P+ foci, microsomal malondialdehyde(MDA) and conjugated diene contents were determined. In addition, cytochrome P450 content and the activities of NADPH cytochrome P450 reductase and glucose 6 phosphatase were also measured. There was no significant effect by gamma irradiation on microsomal MDA content, conjugated diene, cytochrome P450 content and activities of NADPH cytochrome P450 reductase and glucose 6 phosphatase. However with DEN treatment, microsomal MDA content and conjugated diene contents were significantly changed. Cytochrome P450 content was also significantly increased while microsomal glucose 6 phophatase activity was significantly decreased with DEN treatment. However activity of NADPH cytochrome P450 reductase was not affected. An interesting finding in this study was that the number and area of hepatic GST P+ foci of the rats fed gamma irradiated beef were significantly(p<0.05) lower than those of the control. Such a lowering effect on GST P+ foci formation was highest at the dose of 3kGy than others. Overall results suggest that the consumption of low dose of gamma irradiated beef does not affect the formation of lipid peroxide, cytochrome P450 system and membrane stability.

• Journal of Nutrition and Health
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• 제35권6호
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• pp.643-649
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• 2002

This study was done to investigate effects of ${\gamma}$-irradiated pork feeding on the formation of glutathione S-transferase placental form positive (GST-P$^{+}$) foci, lipid peroxidation, cytochrome P450 system and microsomal glucose 6-phosphatase activity in diethylnitrosamine (DEN)-initiated rat hepatocarcinogenesis. Weaning Sprague-Dawley male rats were fed the diet containing ${\gamma}$-irradiated ground pork at the dose of 0, 3, 10, 30 kGy as a 20％ of protein source for 8 weeks. One week after feeding, rats were intraperitoneally injected twice with a dose of DEN (50 mg/kg BW). As a promote.,0.05％phenobarbital was fed in drinking water from one week after DEN treatment until the end of experiment. At the end of 8th week, rats were sacrificed and hepatic GST-P$^{+}$ foci, microsomal malondialdehyde (MDA) and conjugated diene contents were determined. In addition, cytochrome P450 content and the activities of NADPH cytochrome P450 reductase and glucose 6-phosphatase were also measured. There was no significant effect by gamma irradiation on microsomal MDA content, conjugated diene, cytochrome P450 content and activities of NADPH cytochrome P450 reductase and glucose 6-phosphatase. However with DEN treatment, microsomal MDA content showed a increasing tendency. Cytochrome P450 content was also significantly increased while microsomal glucose 6-phophatase activity was significantly decreased with DEN treatment. However the activity of NADPH cytochrome P450 reductase was not affected. An interesting finding in this study was that the number and area of hepatic GST-P$^{+}$ foci of rats fed gamma irradiated pork were tended to be decreased by high dose of irradiation, but were not significantly different. These results might imply that the consumption of low dose of gamma irradiated pork does not affect the formation of hepatic GST-P$^{+}$ foci and lipid peroxide and membrane stability.ability.

• Journal of Nutrition and Health
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• 제36권8호
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• pp.785-792
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• 2003

This study is conducted to determine the effects of dietary source of $\omega$3 fatty acids on preneoplastic foci and the glutathione dependent enzymes in rat hepatocarcinogenesis initiated by diethylnitrosamine (DEN). Male Sprague-Dawley rats were fed one of three diets containing 10% (w/w) fats fixed p/s = -1.0 and $\omega$6/$\omega$3 ratio = -0.4 or 4.0 ; fish oil-com oil blended (FC), com oil-beef tallow-fish oil blended (CF), com oil-beef tallow-perilla oil blended (CP), from gestation period. At 10 weeks, animals of experimental groups were injected intraperitoneally with DEN (200 mg/kg body weight) and two-thirds partial hepatectomy was carried out 3 weeks later and were sacrificed 8 weeks after DEN initiation. The area and number of glutathione S-transferase placenta (GST-P) positive foci were significantly decreased in rats fed diets containing fish oil (FC and CF) than those fed perilla oil diet (CP). Fish oil feeding significantly increased the activities of glutathione dependent enzymes. Rats fed diets containing fish oil (FC and CF) significantly increased the glutathione (GSH) content and the activities of glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST). Glutathione dependent enzymes had significantly negative correlation with GST-P positive foci. Glucose 6-phosphatase (G6Pase) was increased in rats feeding fish oil. Thiobarbituric acid reactive substances were not different among groups. Therefore, the preventive effect against hepatocarcinogenesis might be explained by induction of the glutathione dependent enzymes and G6Pase. (Korean J Nutrition 36(8): 785∼792, 2003)

• Preventive Nutrition and Food Science
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• 제1권2호
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• pp.214-219
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• 1996

This study was done to investigate effects of n-s fatty acids and vitamin E supplement on the preneoplastic hepatic enzyme altered foci and cholesterol metabolism in experimental hepatocarcinogenesis system. Weaning male Sprague-Dawley rats were fed the diet containing either 15% corn oil(CO) or sardine oil(SO) with or without vitamin E 800IU supplementation for 12 weeks. After two weeks of feeding, rats were intraper-itoneally injected with a single dose of diethylnitrosamine(DEN:200mg/kg, BW). At the 4th week, rats were given the diet containing 0.02% acetylaminofluorene(AAF) for next 4 weeks. At the 6th Week, 0.05% pheno-barbital was incorporated into diet for 6 weeks. At the end of 12th week, rats were sacrificed and hepatic glutathions S-transferase placental form positive(GST_{TEX}$P^{+}${/TEX}) foci and serum and liver cholesterol levels were determined. GST_{TEX}$P^{+}${/TEX} formation was significantly decreased by SO feeding when compared with Co feeding but it tended to be enhanced by vitamin E supplementation. Histopathological changes were similar to patterns of GST_{TEX}$P^{+}${/TEX} formation in almost all dietary groups. Serum and hepatic cholesterol levels of SO fed groups were significantly lower than those of CO fed groups. Carcinogen treatments significantly increased serum and liver cholesterol levels in CO fed groups but not in SO fed groups. Correlation data showed a positive correlation(${\gamma}$=0.83, p<0.01) between serum cholesterol level GST_{TEX}$P^{+}${/TEX} foci area. These results indicate that sardine oil as a m-3 fatty acid source may have a reducing effect in rat hepatocarcinogenesis by the altheration of cholesterol metabolism.

• Journal of Nutrition and Health
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• 제38권1호
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• pp.20-29
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• 2005

This study is conducted to determine the effects of dietary levels of corn and tuna oils on the formation of preneoplastic lesions in die-thylnitrosamine (DEN) induced rat hepatocarcinogenesis. Weanling male Sprague-Dawley rats were fed 2.5, 5, 15, 25% (w/w) corn or tuna oils. Hepatocellular carcinogenesis was induced by DEN (200 mg/kg body weight) and two-thirds partial hepactectomy was carried out 3 weeks later and were sacrificed 8 weeks after DEN initiation. Tuna oil group showed smaller area of placental glutathione S-transferase (GST-P) positive foci than com oil group. Com oil group of 25% (w/w) showed the widest area of GST -P positive foci, and tuna oil group showed significantly smaller area of GST-P positive foci than com oil in 25% (w/w) level but had no differences between oil levels. Thio-barbituric acid reactive substances (TBARS) content was the highest in 25% (w/w) level of tuna oil group fed long chain and highly polyunsaturated fatty acids. Also serum ${\gamma}$ -glutamyltranspeptidase (GGT) activities in 25% level of tuna oil group were significantly higher than by other levels. As oil contents increased, glucose 6-phosphatase (G6Pase) seems to decrease in com oil groups but remained the same in tuna oil groups. Glutathione reductase (GR) activities were significantly higher in tuna oil group, and the higher the level of tuna oil, the higher GR activities. But Cu/Zn superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities didn't seem to be influenced by levels and kind of dietary fats. Therefore, as oil levels increased, com oil rich in n-6 fatty acids promoted carcinogenesis but tuna oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) of n-3 fatty acids suppressed. Although lipid peroxidation products were elevated in 25% (w/w) tuna oil group, GST-P positive foci didn't increase. Therefore pre-neoplastic lesions might be reduced through mediation of a lipid peroxidation process in tuna oil. As fat contents of tuna oil increased, elevated GR activities may give a rise to produce more reduced glutathione in order to protect against free radical attack, and high G6Pase activities remained the same and they contributed to membrane stability. So tuna oil diet seems to protect hepatocarcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2257-2261
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• 2012

Pinocembrin (5, 7-dihydroxyflavanone) is a flavanone extracted from the rhizome of Boesenbergia pandurata. Our previous studies demonstrated that pinocembrin had no toxicity or mutagenicity in rats. We here evaluated its effects on the initiation and promotion stages in diethylnitrosamine-induced rat hepatocarcinogenesis, using short- and medium-term carcinogenicity tests. Micronucleated hepatocytes and liver glutathione-S-transferase placental form foci were used as end point markers. Pinocembrin was neither mutagenic nor carcinogenic in rat liver, and neither inhibited nor prevented micronucleus formation as well as GST-P positive foci formation induced by diethylnitrosamine. Interestingly, pinocembrin slightly increased the number of GST-P positive foci when given prior to diethylnitrosamine injection.

• Biomolecules & Therapeutics
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• 제3권4호
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• pp.279-287
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• 1995

This study examined the anti-cancer effects of diallyl sulfide(DAS) and/or diallyl disulfide(DDS), major components of garlic oil, with the DEN-PH model in rats, by the numbers and areas per cm$^2$ of induced glutathion S-transferase placental form(GST-P) positive foci and silver-stained nucleolar organizer regions(Ag-NORs) counts per nuclei in liver as indicator. Sprague-Dawley(SD) rats were given the diethylnitrosamine(DEN, 200 mg/kg, i.p.) as initiator and 2 weeks later, in experiment 1, rats were treated with DAS(200 mg/kg, i.g.) and/or DDS(50 mg/kg, i.g.) for 6 weeks, respectively and concomitantly and also were given the same dose of DAS and/or DDS prior to DEN treatment for 2 weeks, and in experiment II, rats were treated with potential cancer promoter, 2-acetylaminofluorene (2-AAF, 20 mg/kg, i.g.). The DAS and/or DDS were treated prior to 2-AAF for 8 weeks, respectively and concomitantly. Then the anti-promoting effects of DAS and/or DDS were assessed. All rats were subjected to the two-thirds partial hepatectomy(PH) at week 3 and sacrificed at week 8. In experiment I, DAS and/or DDS treatment only prior to DEN showed inhibition of the development of GST-P positive foci. In experiment II, DAS and/or DDS treatment prior to 2-AAF promotion showed obvious inhibition of the development of GST-P positive foci in numbers and areas and AgNORs counts. In conclusion, We found DAS and/or DDS had the preventive effects on the hepatocarcinogenesis in rats and the concomitant treatment had some additive effects compared with the each treatment and AgNORs counts correlated well with the preneoplastic hepatic lesion.

• BMB Reports
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• 제33권6호
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• pp.469-475
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• 2000

The purpose of this study was to examine the chemopreventive potential of taurine at various levels on the diethylnitrosamine (DEN)·induced hepatocarcinogenesis. Male Sprague-Dawley rats were fed on diets containing 0, 1, 2, 3% taurine or 5% ${\beta}-alanine$ for taurine depletion. Then they were treated with DEN and 2/3 partial hepatectomy. The number of placental glutathione S-transferase positive ($GST-P^+$) foci, as a preneoplastic marker in the 1 % taurine group was lower than the control diet group. However the difference was insignificant. Although taurine diets reduced the thiobarbituric acid reactive substance (TBARS) level, the number of $GST-P^+$ foci was increased in 3% taurine diet group. The 1 % taurine diet increased the glutathione (GSH) level and GST activity, however they unfortunately did not suppress the foci formation. In the 3% taurine group, the GSH level and GSH peroxidase (GPx) activity were significantly decreased. Excess taurine supplementation of the pharmaceutical dose worked against hepatic chemoprevention, which might result from modulation of GPx activity and GSH utility. On the contrary, taurine might work as an antioxidant against TBARS production as the 1 % taurine diet increased GSH level. The potency of the cancer preventive effect of taurine still remains and further studies should investigate the effect of taurine with less than 1 % levels on the prevention of hepatic cancer.

• 한국식품위생안전성학회지
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• 제13권1호
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• pp.29-33
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• 1998

의약품과 식품을 포함한 자연이나 환경 속에 포함되어 있는 여러 가지 화학물질들은 암 및 돌연변이를 유발할 수 있기 때문에 이런 것들에 의한 유해작용을 줄이려 노력하고 있으나 완전히 없기에는 어려운 현실이다. 따라서 식생활 습관을 개선하거나 식품 내에 존재하는 발암억제물질은 이용하여 암의 발생을 줄이기 위한 연구는 암의 치료제 개발과 더불어 관심의 대상이 되고 있다. 여러 가지 식품 속에 자연적으로 함유된 ellagic acid는 항돌연변이와 발암억제 효과가 있는 것으로 잘 알려져 있다. 따라서 본 실험에서는 단기간에 ellagic acid의 발암 억제 효과를 알아보기 위하여 전암지표효소인 GST-P 양성증식소를 측정하였다. Diethylnitrosamine으로 간장에서 암을 유발하였고 phenobarbital 과 간부분절제술로 암을 촉진시켰으며, ellagic acid를 400과 800ppm 투여군으로 구분하고 투여시기를 달리하여 실험하였다. 실험결과 암이 유발되기 전부터 실험종료까지 ellagic acid 400 ppm 투여군의 동물에서만 발암 억제효과를 관찰 할 수 있었으나, 800ppm 투여군에서는 투여시기에 관계없이 종양억제효과가 나타났다. 따라서 Diethylnitrosamine으로 유발된 간장의 발암은 ellagic acid에 의해 용량 의존적으로 억제됨을 알 수 있었다.